There is a world-wide search for a therapy that can prevent the complications in type 1 and type 2 diabetes. Chronic exposure to diabetes leads to an increased incidence of microangiopathic complications which are associated with considerable morbidity and mortality. For example, disturbances in the microcirculation of the feet may lead to amputation of the legs which in turn can cause severe complications. In the case of diabetic nephropathy renal failure is usually the actual cause of death. Diabetes is also the most common cause of renal failure among young adults.
The factors that lead to diabetic nephropathy have been extensively studied but are still incompletely known. According to the general concept, early functional effects of diabetes, such as hyperfiltration, are contributing factors. Hyperfiltration is associated with increased glomerular pressure and increased albumin excretion rate (AER). Increased AER is considered to be an early sign of glomerular damage.
The presently most commonly used therapy, ACE inhibitors, will not prevent the development of diabetic nephropathy, but may postpone the development of terminal renal failure.
It has been disclosed that nitecapone, a COMT inhibitor has a natriuretic effect (Eklof et al. J. Am. Soc. Nephrology 5 (3), 657, 1994, Holtback et al., J. Am. Soc. Nephrology, 7(9), 1633, 1996). However, the effect of COMT inhibitors on hyperfiltration and albuminuria has not been suggested earlier.